Fentanyl Buccal Tablets for Breakthrough Pain in Highly Tolerant Cancer Patients: Preliminary Data on the Proportionality Between Breakthrough Pain Dose and Background Dose

Abstract

Context. Cancer patients receiving high doses of opioids as background medication are challenging, and it would be useful clinically to know whether a rapid-onset opioid (ROO) for breakthrough cancer pain (BTcP) may be started at a dose proportional to the background opioid dose.Objectives. The aim of this study was to assess the efficacy and safety of the fentanyl buccal tablet (FBT) in doses proportional to the opioid dose administered for background analgesia in a sample of patients with BTcP who were receiving high doses of opioids.Methods. Twelve patients who were receiving opioids for background analgesia at doses equivalent to more than 500 mg of oral morphine and had adequately controlled pain were prospectively recruited. BTcP was treated with proportional doses of FBT: patients receiving 600 mg of oral morphine equivalents were administered 1000 mg of FBT, patients receiving 900 mg of oral morphine equivalents were administered 1500 mg of FBT, and so on. For each episode of BTcP, trained nurses collected pain intensity (on a 0e10 numerical rating scale) and emerging problems when called for increases in pain considered to be severe in intensity by patients (T0) and 15 minutes after FBT administration (T15).Results. Patients were receiving mean doses of oral morphine equivalents of 1340 mg (AE585; range 720e2400). Seventy-nine events were treated with FBT (6.6 AE 4.9 for each patient). The median pain intensity of BTcP events was 8 (range 7e10), and the mean dose of FBT administered was 2233 mg (AE975; range 1200e4000). In most events, a decrease in pain intensity >33% and >50% was observed (n ¼ 14 and n ¼ 48, respectively) 15 minutes after the administration of FBT. Data on 11 episodes were missed. Only six events were unsuccessfully treated. In all the patients, the level of adverse effects after FBT administration was mild and indistinguishable from that associated with the background opioid analgesia. Conclusion. FBT in doses proportional to the high doses of opioids used for background analgesia was efficacious and well tolerated when administered for BTcP. Controlled studies with a specific design and a large number of patients should confirm such preliminary results. J Pain Symptom Manage 2011;42:464e469.

The use of fentanyl buccal tablets for breakthrough pain by using doses proportional to opioid basal regimen in a home care setting

“…These findings confirm preliminary observations in patients admitted to hospital units who were receiving high doses of opioids for background analgesia and who were effectively treated with proportional doses of FBT, without adding risks of occurrence of adverse effects [21]. As this approach could not be generalized due to the characteristics of the unit, this hypothesis was tested in another setting, like home care.…”

“…In addition, patients who had unstable background analgesia or more than four episodes of BTP/day were excluded. The criterion to define BTP was reported in previous studies [6,12,14,21]. From this sample, patients who were receiving opioids in doses of oral morphine equivalents equal or more than 60 mg daily were prescribed FBT in doses proportional to opioids used for background analgesia.…”

“…The use of proportional doses has been shown to be safe and effective in a large number of patients in several open-label and controlled studies [16][17][18][19][20]. FBT given even at high doses proportional to the opioid doses used for background analgesia was safe and effective [21]. This data was explained by the high level of tolerance achieved by patients receiving high doses of opioids for background analgesia.…”

Intranasal Fentanyl Versus Fentanyl Pectin Nasal Spray for the Management of Breakthrough Cancer Pain in Doses Proportional to Basal Opioid Regimen

“…24 No preference for 1 of the 2 products was given by patients who received both delivery systems. The other important finding is that both treatments in doses proportional to the basal opioid dose used for background pain were effective as well as tolerable, confirming experience accumulated through the years and the findings of some controlled studies, [13][14][15][16][17][18][19][20][21][22][23][24] even when higher doses were used. Finally, despite a similar analgesic trend, FPNS had a major impact at the intervals taken into consideration.…”

“…For instance, the only existing controlled study performed using a fentanyl buccal tablet has evidenced that proportional doses are more effective than the dose titration approach, without higher risks of adverse effects, 22 confirming a series of open-label studies in which proportional doses were highly effective and well tolerated. [13][14][15][16][17][18][19][20][21][22][23][24][25] Finally, there is clinical legend suggesting that the rescue dose of opioids for BTP should be 10% of the daily dose of scheduled opioids. Several studies of proportional doses have shown that to produce meaningful and clinical analgesic effects, it is necessary to administer 15 to 20% of the daily dose.…”